Acute effects of glibenclamide on reactive hyperaemia in the lower limbs in humans

Article type: Research Article

Authors: Capecchi, P.L. | Guideri, F. | Colafati, M. | Acampa, M. | Cuomo, A. | Lazzerini, P.E. | Pasini, F. Laghi

Affiliations: Department of Clinical Medicine and Immunological Sciences, Section of Clinical Immunology, University of Siena, Siena, Italy

Note: [] Corresponding author: Pier Leopoldo Capecchi, Istituto di Semeiotica Medica, U.O. Immunologia Clinica, Università di Siena, Policlinico “Le Scotte”, 53100 Siena, Italy. Tel.: +39 0577 585741/585744; Fax: +39 0577 44114; E‐mail: capecchipl@unisi.it.

Abstract: Three episodes of 1 min ischemia in the lower limbs in humans reduced the metabolic debt repayment (expressed as AUC of reactive hyperaemia) following more prolonged ischemia (666.6±86.6 vs 500.0±33.5 ml/100 ml). The administration of the ATP‐dependent K+ channel blocker glibenclamide was associated with a significant reduction in the AUC of reactive hyperaemia (666.6±86.6 vs 563.1±76.6 ml/100 ml), and with the removal of the protective effect produced by 3 episodes of 1 min ischemia (563.1±76.6 vs 551.8±71.3 ml/100 ml). Plasma level of glibenclamide reached the peak value of 1.295±0.15 μmol/l 2 h after drug administration, ranging around the 1 μmol/l concentration in the following 3 hours. Our findings produce indirect evidence that, similarly to the ischemic preconditioning of the heart, the protective effects towards ischemia of brief repeated episodes of sub‐maximal occlusion in the peripheral circulation of the lower limbs in humans are mediated by ATP‐dependent K+ channels.

Journal: Clinical Hemorheology and Microcirculation, vol. 27, no. 2, pp. 77-82, 2002